PROJECT SUMMARY Neuropathic pain is a disabling pain syndrome caused by a lesion or disease of the somatosensory system.14 For example, postherpetic neuralgia, trigeminal neuralgia, diabetic neuropathy, amputation, and peripheral nerve injury are all associated with neuropathic pain.14 For patients with neuropathic pain refractory to medical therapy, modulation of specific neural structures in the central or peripheral nervous system, can provide effective alternative treatments.12,13 Dorsal root ganglion (DRG) stimulation is an approved therapy for complex regional pain syndrome (CRPS). The current FDA-approved device on the market for DRG stimulation is generally considered safe, but has been associated with complications such as pulse generator infections and lead migration.17, 18 Our overall goal is to provide a novel, minimally-invasive, and effective treatment for patients with refractory neuropathic pain. We propose a wireless millimeter-sized nerve stimulator that can be delivered through the vasculature and stimulate the DRG. This transformative ?endovascular nerve stimulation? (EVNS) technology would have major advantages compared to state-of-the art nerve stimulation therapies for pain. This new concept for pain treatment using these small wireless endovascular stimulators is enabled by the development of magnetoelectric (ME) materials for wireless power delivery to bioelectronic devices.3 The goal of this project is to develop a wireless endovascular magnetoelectric nerve stimulator to stimulate the dorsal root ganglion and alleviate the symptoms of neuropathic pain. Successful completion of this project will establish proof-of-principle and provide early safety/efficacy data on wireless endovascular DRG stimulation for treatment of refractory neuropathic pain. Based on the successful demonstration of DRG stimulation, we will be able to develop EVNS therapies for other neuropathic pain targets. While in this proposal we focus on the treatment of CRPS, successful demonstration of EVNS will provide a platform technology for treating numerous other neuropathic pain syndromes. At the end of the 3-year period, we plan to submit for FDA clearance and to follow with a first in human study and a subsequent clinical trial to test the safety and efficacy of wireless endovascular DRG stimulation in patients with refractory neuropathic pain.